Ki-ras oncogene and p53 tumour suppressor gene mutations in colorectal carcinomas from the European Saar-Luxembourg region are less frequent than predicted by the classic adenoma-carcinoma sequence model.
Recent investigations of colorectal cancer (CRC) have suggested that the accumulation of specific alterations in cell-growth regulating genes trigger the stage-wise progression to malignancy and that at least some of them could be useful for prognosis. In this study, the frequency, location and type of mutations of the Ki-ras proto-oncogene exons 1-2 and p53 tumour-suppressor gene exons 5-9 were analysed in colorectal carcinomas of 72 patients from the European Saar-Luxembourg region using PCR-SSCP screening and direct sequencing. The incidences of Ki-ras activating and p53 inactivating point mutations in these European samples were much lower (Ki-ras: 5 (6.9%) and p53: 13 (18.1%)) than reported for both genes in American studies (40-50% at least) (P < 1 x 10(-3)). These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.
Pauly
M
M
Laboratoire de Recherche sur le Cancer et les Maladies du Sang (RCMS), Centre Universitaire de Luxembourg, Grand Duchy of Luxembourg, Germany.
Schmitz
M
M
Kayser
I
I
Türeci
O
O
Lagoda
P
P
Seitz
G
G
Dicato
M
M
D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005858:Germany; D006801:Humans; D008189:Luxembourg; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D012004:Rectal Neoplasms / Q000235:genetics*